Abstract

Background IgG4-related disease (IgG4-RD) is a distinct clinical entity characterized by fibro-inflammatory lesions rich in IgG4+ plasma cells in different organs and often - elevated serum IgG4 level. The cornerstone of the diagnosis is unique histopathological features of the lesion. The first-line treatment are glucocorticoids in average dose of 0,6 mg/kg. However, this treatment is associated with many toxicities and high level of relapses during tapering. It was shown that B-cell depletion could be a very beneficial strategy in IgG4-RD.

Objectives To report our experience of Rituximab (RTX) treatment in IgG4-RD to evaluate its efficiency and safety.

Methods Ten patients with biopsy-proven IgG4-RD were included. The spectrum of involved sites and efficiency of the treatment was evaluated by clinical examination and imaging studies (chest and/or abdomen CT, ultrasound of orbits/lacrimal glands and major salivary glands). IgG4 was measured at baseline and 3-12 months after RTX treatment. RTX was administrated in two 1000mg doses on days 0 and 15, or four 500mg doses on days 0-7-14-21. Repeat courses were conducted in 4-6 months after the previous course, in repeat courses RTX was administrated in a single 500mg dose.

Results Ten patients with mean age 45.2 years (range 24-78) were included. The mean age of the manifestation of IgG4-RD was 38.9 years (range 24-77). The mean time to diagnosis was 73.6 months (range 5-204), the mean number of organs involved was 2.5 (range 1-5). Eight patients (80%) had elevated serum IgG4 levels. For those patients mean was 11.1 g/l (range 2.6-28.1). Five patients (50%) had treatment prior to RTX administration: methylprednisolone pulse-therapy - 1, multiple COP/CHOP courses – 2, high-dosage IV cyclophosphomide – 2. Four of these five patients were administrated RTX because of inefficiency of the treatment (progression of the symptoms), 1 – relapse during treatment tapering. All patients were followed for 3-28 months after RTX administration. Three patients (30%) received 1 course of RTX, the rest (70%) – from 2 to 4 courses. All repeat courses were for remission maintenance. All patients were administrated methylprednisolone 4-8mg per day as well. The majority of patients (90%) were able to discontinue oral glucocorticoids in 3-12 months after first course of RTX. Significant clinical improvement was observed in eight patients (80%) within 1-3 months after first course of RTX (disappearance of: eyelids swelling, exophtalmia, massive enlargement of salivary glands,hydronephrosis and nasal congestion). In all patients, the clinical improvement was supported with imaging studies. In two patients, stabilization of the process was observed. IgG4 serum level was decreased to normal values in 5 patients within 3 months after the first course of RTX. In seven patients followed for 12 months and more there were no flares, possibly due to repeat courses of RTX. All courses were well tolerated. There were four cases of side-reactions in three patients: in 1 patient total IgG decreased without infectious consequences, 1 patient had a flare of chronic sinusitis and 1 patient had moderate infusion reaction (bronchospasm) and pneumonia.

Conclusions RTX is efficient and well-tolerated treatment and should be considered as a good alternative for toxic glucocorticoid therapy, which currently, is prevalent.

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